(P22-066-25) Molecular Approaches to Hypertension Diagnosis Based on Metabolite Risk Score Developed Through Metabolomics

Objectives: Hypertension is traditionally diagnosed based on systolic and diastolic blood pressure (BP) measurements. However, due to its asymptomatic nature, it is challenging to predict and diagnose early, prior to the onset of clinical symptoms. Therefore, the present study was aimed at developing a metabolite risk score (MRS) using key biomarkers to aid in the diagnosis of hypertension.

Methods: A total of 100 plasma samples (n=50; healthy individuals; and n=50; hypertension patients) were collected for the discovery phase to establish the MRS. An additional 100 plasma samples, grouped in the same manner as the discovery set, served as an independent validation set to assess the MRS function. Metabolomics (UHPLC-MS/MS) was performed to identify key metabolites. The MRS was calculated using the equation ∑β_iM_i, where β_i represents the β coefficient (linear regression) that incorporates the key metabolites, and M_i denotes the z-score of each key metabolite.

Results: A total of 60 metabolites were identified in the discovery set via UHPLC-MS/MS. Among these, six metabolites were selected as major metabolites based on: 1) a VIP score ≥1.5, and 2) a FDR-adjusted p-value < 0.05. After further examination to determine their potential in diagnosing hypertension, Glu-Leu and phenylacetylglutamine were identified as key metabolites. The MRS, calculated with the equation ∑β_iM_i, demonstrated 95.5% (p < 0.001) of diagnostic accuracy for hypertension in the discovery set, compared to 82.4% (p=0.002) for systolic BP and 77.2% (p=0.010) for diastolic BP. In the validation set, the MRS showed nearly identical diagnostic accuracy (95.6%, p < 0.001), showing significantly better efficacy than systolic and diastolic BPs, which had diagnostic accuracy of 68.6 % (p=0.065) and 70.8 % (p=0.039), respectively.

Conclusions: By considering the effects of various key biomarkers through weighted methods, the MRS may offer more effective diagnostic approaches compared to conventional methods or the use of individual significant biomarkers. In conclusion, the present study suggests that molecular diagnostic approaches for hypertension, using MRS, may serve as a promising aid for hypertension diagnosis.

Funding Sources: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT; Ministry of Science and ICT) [NRF-2022R1A2C1093361].